Halogenated organic compounds represent an important group of chemicals that have found use in a wide array of research, medical and industrial applications. This raises the question as to which analytical techniques are most suitable for detecting and monitoring in real-time these compounds in the environment. To provide underpinning information on the potential use of chemical ionisation mass spectrometric techniques, we present here details of a selective reagent ion-time-of-flight-mass spectrometry (SRI-ToF-MS) fundamental study characterising the reactions of O2+• with six common halogenated organic compounds, namely, 2,2,2-trifluoroethanol (TFE, CF3CH2OH), 1,1,1,-trifluoroacetone (TFA, CH3COCF3), 1,1,2,2-tetrafluoro-3-methoxypropane (TMP, CHF2CF2CH2OCH3), 1,1,1,3,3,3-hexafluoro-2-methoxypropane (isoflurothyl, (CF3)2–CHO–CH3)), 2-chloro-1,1,2-trifluoro-1-methoxyethane (CTME, CH3OCF2CHFCl) and 1-ethoxy-1,1,2,2-tetrafluoroethane (ETE, CH3CH2OCF2CHF2). We investigated the distributions of the product ions as a function of the reduced electric field strength (E/N) between 65 Td and 205 Td. Five of the halogenated organic compounds generated rather simple product ion distributions. Only one, non-halogenated product ion resulted from each of the reactions of O2+• with TFE (CH2OH+), TFA (CH3CO+) and TMP (CH3OCH2+). For the other two out of the first five compounds, isoflurothyl and CTME, three product ions were observed, but only one of these was dominant with a product ion branching percentage of ∼80% throughout the reduced electric field range investigated: C3H4F3O+ resulting from isoflurothyl and C2H3F2O+ from CTME. The sixth compound, ETE, displayed a much richer reaction ion chemistry than the other five compounds. A total of eight product ions were identified, two of which dominated over most of the investigated E/N range, namely C4H5F4O+ and C2H5+. The potential chemical pathways that lead to the formation of the major and minor observed product ions are discussed for all six compounds. We show that SRI-ToF-MS is a useful technique to study the reactions of halogenated organic compounds with O2+•. Its potential use for monitoring TFE, TFA and TMP is limited because the single product ion observed for each of these volatiles is not sufficiently specific and thus characteristic to the originating compound (i.e., reactions of O2+• with non-halogenated organic compounds will also result in the same product ions). However, SRI-ToF-MS could be considered as a potential analytical tool to detect and monitor isoflurothyl, CTME and ETE, as the fluorinated product ions resulting from their reactions with O2+• allow for their detection with a high level of analytical confidence.